Sedibe, AmogelangSibiya, Ntethelelo HopewellNyakudya, Trevor TapiwaGamede, Mlindeli2025-11-242025-11-242025-12Sedibe, A., Sibiya, N., Nyakudya, T. et al. 2025, 'The impact of the recent HIV non-nucleoside reverse transcriptase inhibitors and nucleoside reverse transcriptase inhibitors-based regimens on metabolic health outcomes : a narrative review', Biochemistry and Biophysics Reports, vol. 44, art. 102345, pp. 1-16, doi : 10.1016/j.bbrep.2025.102345.2405-5808 (online)10.1016/j.bbrep.2025.102345http://hdl.handle.net/2263/105447DATA AVAILABILITY : No data was used for the research described in the article.The global prevalence of human immunodeficiency virus (HIV) has led to a significant rise in the chronic use of antiretroviral (ARV) drugs, both for HIV management and pre-exposure prophylaxis (PrEP), to meet the set Joint United Nations Programme on HIV/AIDS (UNAIDS) 95-95-95 targets. Although antiretroviral therapy (ART) has remarkably increased the life expectancy of people living with HIV (PLHIV), it has also been associated with metabolic complications, particularly in glucose and lipid metabolism. Notably, the development of type two diabetes mellitus (T2DM), accounting for 90–95 % of diabetes cases, often stems from an asymptomatic prediabetic state, frequently left undiagnosed. In this narrative review, we address the limited understanding of how prediabetic individuals respond to chronic exposure to antiretroviral therapy. The scope of this review focuses on selected markers of pancreatic metabolic dysfunction, the interplay between modern ARV therapies and prediabetes will be examined. In efforts to enhance and further expand the understanding of potential risks and outcomes of ARVs on metabolically compromised individuals. Through a comprehensive synthesis of existing literature and novel findings from the animal model, in vitro studies and clinical studies, we aim to provide valuable insights for both the scientific and clinical communities, contributing to the optimization of HIV treatment strategies and the mitigation of associated metabolic complications. Based on the available literature, it is evident that more research is needed to better understand the interaction between prediabetes and ART in HIV-infected individuals, to simultaneously reach the set UNAIDS 95-95-95 HIV/AIDS targets and combat the rising trend of noncommunicable diseases in HIV-infected populations. HIGHLIGHTS • The HIV-ART is one of the most effective medications in HIV infection management. • The role of the current HIV-ART on carbohydrate metabolism. • HIV-ART has been previously associated with changed metabolic complications. • The prediabetes as a significant factor in the interplay between HIV and diabetes. • The impact of HIV-ART on pancreatic function and future research on HIV-ART and pancreatic β-cells function.en© 2025 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).Human immunodeficiency virus (HIV)Antiretroviral (ARV)Antiretroviral therapy (ART)People living with HIV (PLHIV)Type two diabetes mellitus (T2DM)HIV-antiretroviral therapyHIV-fixed-dose combination therapyPrediabetesDrug-metabolic complicationsPancreatic health outcomesArticle